Studies of the cell lineage of the effector cells that spontaneously lyse HSV-1 infected fibroblasts (NK(HSV-1))

Natural killer (NK) cells that lyse herpes simplex virus-type 1- (HSV-1) infected fibroblasts (NK(HSV-1)) have been under study because they are thought to play an important role in host defense against herpes virus infections. Studies were undertaken of certain patient groups in order to help characterize these cells and develop evidence about the cell lineage to which these effector cells belong. Our studies of bone marrow transplant recipients indicate that this function is derived from bone marrow stem cells, because engraftment of patients demonstrating low NK(HSV-1) before transplantation with marrow from normal matched siblings resulted in chimeras with normal NK(HSV-1) responses. NK(HSV-1) was also found to be dependent on a normal bone marrow, because patients with juvenile osteopetrosis, an inherited disorder resulting in obiteration of the marrow cavity by solid bone, had very low responses. Further, 15 of 17 patients with aplastic anemia (AA) and complete marrow failure also showed very low NK(HSV-1) responses, whereas nine of 11 AA patients with some evidence of bone marrow precursors had normal responses. Our studies of patients with various immunodeficiency diseases indicate that the NK(HSV-1) effector cells do not belong to the lymphoid lineage of hemopoietic cells. Thus, four patients with severe combined immunodeficiency disease (SCID) had normal NK(HSV-1) responses even though their lymphoid cell numbers and functions were grossly deficient. In addition, two of these SCID patients also demonstrated NK(HSV-1) responses without evidence of pre-T cells in their marrow, indicating that these effectors are not pre-T cells. Studies of patients with monocyte/granulocyte lineage dysfunctions were less conclusive. Some patients with abnormalities (AA and Wiskott-Aldrich syndrome) also demonstrated NK(HSV-1) deficiencies. In contrast, patients with chronic granulomatous disease and certain SCID patients had normal NK(HSV-1) in spite of dysfunctions of the monocyte/granulocyte series. Although NK(HSV-1) effectors may be related to the precursors of the monocyte/granulocyte series, it is equally possible that these cells belong to an independent hemopoietic cell lineage.